This is a Career Development Award proposal for Dr. Annette Fleckenstein. She is an Associate Professor of Pharmacology and Toxicology at the University of Utah. She has been active in drug abuse research for 10 years and has made important contributions to elucidating the effects of psychostimulants on dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) regulation and function, especially as related to the neurotoxic effects of the amphetamines. The applicant currently devotes 50% of her time to research while 50% of her effort is occupied by teaching, department, and college activities. This Career Development Award will allow the applicant to increase her research effort to 75%; substantially increasing her research flexibility and allow her to fully take advantage of her scientific skills as she becomes established as a leader in her academic field. During the time of support by this award, she will direct research which tests the following principal hypotheses: 1) differences in the effect of METH and cocaine on VMAT-2 and DAT contribute to their unique persistent DA consequences; and 2) methylphenidate affects vesicular DA transport and the intraneuronal localization of VMAT-2 in a manner distinct from amphetamine. The increase in research time resulting from a Career Development Award will not only allow the applicant to expand upon these studies, but also develop expertise in technologies new to her laboratory, including liquid chromatography-mass spectrometry to explore the hypothesis that METH-induces formation of differentially modified DAT oligomers. The increase in research time will also allow the applicant greater opportunity to participated in interdisciplinary efforts such as those involving the Utah Addiction Center (a translational center).